Ketone and Hawthorn Extract Supplementation in Congestive Heart Failure

Not Applicable

• Conditions: Congestive Heart Failure(CHF)

• Registration Number: NCT07166965
• Lead Sponsor: Thomas Jefferson University

Brief Summary

The purpose of this research is to gain a better understanding of whether supplements can improve heart health. There are a number of study procedures and tests that will occur as a part of the research study. There are 3 groups or arms in the study: one group will receive a ketone supplement, one group will receive hawthorn and a third group will receive a placebo that does not contain ketones or hawthorn. The purpose of the study is to learn whether these supplements improve heart heath in patients who have congestive heart failure.

Participants will not know which supplement is received. The study doctor will know. This is called a single blind study. The supplements will provided along with instructions and educational materials. The duration of taking the supplements is approximately 8 weeks and full participation in the study is approximately 3 months. Participants with congestive heart failure will be enrolled through Jefferson Health in Philadelphia, Pennsylvania.

Detailed Description

This is a Randomized, placebo-controlled single blind pilot study; the duration of the study enrollment is 24 months. It will be conducted at Thomas Jefferson University, Departments of Integrative Medicine, and Nutritional Sciences; Department of Cardiology. Locations: Marcus Institute Centers of Integrative Health at Villanova and Center City Philadelphia. The enrollment goal is 45: 15 in each study arm, ketone, hawthorn extract, or placebo. The investigators will increase each arm by three for a total of 54 to allow for attrition and early withdrawals. Participants will receive a commercially available Hawthorn extract or nutritional ketone monoester, or placebo.

The Investigators will enroll patients with a diagnosis of stable, ambulatory heart failure, classified by the New York Heart Association (NYHA) as functional Class II or III by their cardiologist and/or by the Principal Investigator.

Study Timeline

• Study First Submitted: 2025-07-30
• Status Verified: 2025-09
• Study Start: 2025-09-01
• Study First Submitted QC: 2025-09-02
• Last Update Submitted: 2025-09-02
• Study First Posted: 2025-09-11
• Last Update Posted: 2025-09-11
• Primary Completion: 2029-09
• Study Completion: 2029-09-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• Equal to or greater than 18 years of age
• Diagnosis of heart failure and be classified as NYHA Class II or III either pre-enrollment or at the time of enrollment: Class II - Patients with cardiac disease resulting in slight limitation of physical activity who are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, or dyspnea (shortness of breath or difficulty breathing).

Class III - Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea (shortness of breath or difficulty breathing).

• Stable guideline directed medical therapy for at least 1 month prior to enrollment, including no changes in maintenance diuretic dosing
• Taking appropriate guideline directed medical therapy as determined by the investigator, who is a heart failure specialist.

Exclusion Criteria

• Patients with Type I DM

• No metal in the body that would prevent undergoing an MRI scan. This includes pacemakers, stents and non-titanium implants that would be contraindicated for an MRI.

• Atrial fibrillation

• Inability to exercise on a treadmill.

• Moderate or greater valvular disease: a condition where the valves of the heart do not function properly.

• Anemia with Hemoglobin <10 g/dL.

• Daily insulin use

• Hypertrophic, infiltrative, or inflammatory cardiomyopathy (a group of heart muscle diseases where the heart muscle becomes abnormally thickened (hypertrophic), invaded by abnormal substances (infiltrative), or inflamed (inflammatory), which can lead to impaired heart function and potential complications like arrhythmias and heart failure.

• Pericardial disease: a general term for conditions that affect the pericardium, the sac that surrounds the heart. Pericardial diseases include pericarditis, pericardial effusion, cardiac tamponade, and constrictive pericarditis..

• Current angina due to clinically significant obstructive epicardial coronary disease. a condition where the major coronary arteries on the surface of the heart (epicardial arteries) become significantly narrowed due to plaque buildup, restricting blood flow to the heart muscle, often causing chest pain and potentially leading to a heart attack.

• Acute coronary syndrome (ACS) refers to a group of conditions where blood flow to the heart is suddenly reduced, causing chest pain or discomfort.

• Coronary intervention within the past 2 months is a medical procedure used to treat ACS by opening a blocked coronary artery, typically done through a minimally invasive technique called percutaneous coronary intervention (PCI).

• Primary pulmonary arteriopathy is also known as pulmonary arterial hypertension (PAH) or primary pulmonary hypertension (PPH), a rare disorder that causes high blood pressure in the pulmonary arteries.

• Known clinically significant lung disease defined as:

  1. Current use of supplemental oxygen, aside from nocturnal O2 for the treatment of obstructive sleep apnea
  2. The use of steroids/antibiotics within the past 6 months for an acute exacerbation of obstructive pulmonary disease
  3. Proximal pulmonary function test (PFT) indicating severe obstructive disease, defined as an FEV1<50% predicted in the context of an FEV1/FVC ratio of <0.70 ("Stage III COPD according to GOLD Criteria: significantly reduced lung function and often accompanied by noticeable symptoms like increased breathlessness, frequent exacerbations, and reduced exercise capacity). (note: only to be used if the subject had PFTs prior to screening)
  4. Proximal 6-minute walk test during which the subject experienced desaturation (<94%) without subsequent normal study.

• Ischemia on stress testing without subsequent revascularization or left heart catheterization showing non-obstructive epicardial coronary disease.

• Significant liver diseases impact on synthetic function or volume control.

• Uncontrolled hypertension: BP >180/110 at baseline.

• Estimated glomerular filtration rate (eGFR) eGFR <30 mL/min/173m2 indicating reduced kidney function

• Creatinine level of Cr >2.5 (2.5 mg/dL) is an indicator of stage 2 chronic kidney disease (CKD).

• Current Alcohol dependence

• Current substance use disorder.

• Chronic narcotic use that cannot be interrupted

• Pregnant or lactating females

• Subject has a medical, mental or psychiatric disorder or physical condition that could reasonably be expected to interfere with the assessment of cardiac symptoms, or with any of the study assessments or study procedures including the PET-MRI imaging, VO2 Max, Echocardiogram ultrasound, blood samples that would put the study participant at great risk.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Primary Outcome Measures

Name	Time	Method
Measure and Compare Changes in Myocardial Function: exercise capacity	From baseline enrollment evaluations with functional measures to the end of supplementation at 8 weeks and evaluations afterwards at weeks 10 to 12.	Compare outcomes of functional measures - exercise capacity as measured by oxygen consumption at peak and anaerobic threshold (VO2peak and VO2at) and exercise duration.; Exercise capacity is measured objectively through laboratory Cardiopulmonary Exercise Tests (CPETs) combined metrics which use equipment to monitor heart rate, breathing, and oxygen consumption; with VO2 peak setting the ceiling for endurance and VO2AT.; Exercise capacity, measured by oxygen consumption (VO2), to measure the body's ability to take in and use oxygen during exercise, with VO2 peak representing the maximum capacity reached and VO2 at the anaerobic threshold (VO2AT) at rest and during peak exercise following approximately 2 months of receiving the respective supplementation or placebo.
Measure and Compare Changes in Myocardial Function: Structure and heart function	From baseline enrollment evaluations with functional measures to the end of supplementation at 8 weeks and evaluations afterwards at weeks 10 to 12.	Compare outcomes of functional measures as measured by changes in myocardial function (evaluate the structure and function of the heart and blood vessels) at rest as measured by Cardiac Magnetic Resonance Imaging (cMRI) indexes of Left ventricular ejection fraction (LVEF) and Right Ventricular Ejection Fraction (RVEF) and myocardial performance at peak exercise (cardiac output \[CO\] and LVEF) as measured by echocardiogram at rest and during peak exercise following approximately 2 months of receiving the respective supplementation or placebo.

Secondary Outcome Measures

Name	Time	Method
Measure and Compare Changes Associated with Supplementation using FDG PET and Cardiac MRI	From baseline enrollment evaluations with functional measures to the end of supplementation at 8 weeks and evaluations afterwards at weeks 10 to 12.	Compare changes associated with the respective nutraceutical supplementation in cardiac glucose uptake as measured by Fluoro deoxy glucose Positron Emission Tomography (FDG PET) and cardiac function as measured by cardiac MRI.
Measure and Compare Changes Associated with Cardiac Metabolism using FDG PET and Cardiac MRI	From baseline enrollment evaluations with functional measures to the end of supplementation at 8 weeks and evaluations afterwards at weeks 10 to 12.	Compare changes associated with the respective nutraceutical supplementation in cardiac glucose uptake as measured by Fluoro deoxy glucose Positron Emission Tomography (FDG PET) and cardiac function as measured by cardiac MRI.

Trial Locations

Locations (1)

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States